The objective of this proposal is to investigate whether fructose-sweetened beverages trigger low-grade systemic inflammation in healthy men and women. Low-grade systemic inflammation, specifically elevated plasma concentrations of C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). While it is known that obesity is associated with inflammation, the causes of low-grade inflammation in humans are not well understood. In a pilot study, the consumption of large amounts of fructose-, but not glucose- or aspartame- sweetened beverages potently induced low-grade inflammation in healthy, lean, young men and women in as little as 8 days. We propose to extend these findings by (a) enrolling a greater number of subjects, (b) enroll obese as well as non-obese subjects, and (c) include a beverage that is sweetened with high fructose corn syrup (HFCS). HFCS is one of the primary sugars consumed in the United States, and a major source of dietary fructose. Our primary specific aim is to assess whether the consumption of fructose- or HFCS- sweetened beverages promotes systemic low-grade inflammation, as measured by plasma concentrations of CRP and IL-6. We hypothesize that plasma CRP and IL-6 concentrations will be elevated after consumption of fructose-containing beverages (fructose and HFCS) when compared to the glucose- and aspartame-sweetened beverages. Our secondary specific aim is to assess whether the consumption of fructose- or HFCS-sweetened beverages lowers plasma adiponectin concentrations. Specifically, we hypothesize that total and high molecular weight (HMW)-adiponectin concentrations in fasting plasma will be lower after subjects have consumed the fructose- or HFCS-sweetened beverages, compared to the glucose- or aspartame-sweetened beverages. We will recruit 12 obese (BMI >30 kg/m2) and 12 non-obese (BMI <30 kg/m2) men and women who are free of chronic inflammatory or metabolic disease. In a double-blind, randomized cross-over design, each subject will complete four 8-day standardized dietary periods that will differ only in the type of sweetened beverage administered. Specifically, subjects will be asked to drink four servings of a beverage each day that is sweetened with aspartame, glucose, fructose, or HFCS (55% fructose, 45% glucose). All solid food will be provided for each of the four 8-day diet periods, and will be consumed ad libitum. Following each dietary period, we will collect fasting blood to measure markers of systemic inflammation and plasma concentrations of total and HMW-adiponectin. This study has the potential to identify a dietary trigger of low-grade inflammation, a likely contributor to CVD and metabolic diseases. The public health impact of this project might be considerable given that the consumption of fructose in the population is pervasive, and is modifiable on an individual as well as a population level. PUBLIC HEALTH RELEVANCE: People with chronic low-grade inflammation have a higher risk for certain diseases such as cardiovascular disease or type 2 diabetes. While it is known that obese people are more likely to show signs of low-grade inflammation than lean individuals, it is unclear what causes this inflammation. In the proposed study, we will investigate whether the sugar fructose, when consumed in a sweetened beverage, triggers low-grade inflammation in healthy men and women compared with other caloric and non-caloric sweeteners.